USPIO-related T1 and T2 mapping MRI of cartilage in a rabbit model of blood-induced arthritis: a pilot study.

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5 T MRI. All rabbits had USPIO (35-75 µmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differences were observed between pre- and post-USPIO T2 values at weeks 5 (P = 0.06) and 10 (P = 0.02), but only with the administration of high USPIO doses in the arthritic group using the conventional method. No significant differences were noted between pre- and post-USPIO T1 values at any imaging time points. Cartilage T2 maps with short-TR and conventional protocols provided similar T2 values [(decreased trend)] (P > 0.05). Concomitant use of USPIO to T1 and T2 mapping of cartilage would not impair the identification of interval changes of T1 and T2 maps. Rapid T2 map provides similar results compared to conventional method, but its validation warrants further investigation.

Quantitative MR imaging evaluation of the cartilage thickness and subchondral bone area in patients with ACL-reconstructions 7 years after surgery.

OBJECTIVE: To evaluate the cartilage thickness (ThC) and subchondral bone area (tAB) of the operated and contra-lateral non-operated (healthy) knees in patients with anterior cruciate ligament (ACL)-reconstruction 7 years after surgery using a quantitative and regional cartilage MR imaging (qMRI) technique. METHODS: Charts of 410 patients with ACL-reconstructions were retrospectively reviewed. Fifty-two patients (male/female, 28/24; mean age, 33.3 years) were included. Patients underwent KT-1000 testing and qMRI of both knees using coronal fat-saturated 3D spoiled gradient-recalled echo (SPGR) sequences (TR/TE, 44/4 ms) at 1.5 T. Quantitative analyses of ThC and tAB in the femoro-tibial cartilage plates were performed using a subregional approach. In addition, qualitative and quantitative assessment of femoral condyle shapes was performed. t tests with Bonferroni corrections were used for statistical analysis of side-to-side differences between the operated and non-operated knees. RESULTS: KT-1000 testing was abnormal in 3/52 patients (6%). Lateral femoral tAB was significantly lower (-9.2%), and medial tibial tAB was significantly larger (+2%) in the operated vs non-operated knee (P<0.001). Regional and subregional ThC side-to-side differences were less than 0.1mm and, except for the external lateral femoral subregion, they were not statistically significant. Flattened and broader shapes of medial femoral condyles (P<0.001) were found in operated knees. No significant association of presence of cartilage or meniscus lesions at surgery with ThC 7 years post-operatively was found (P=0.06-0.98). CONCLUSION: There is evidence for changes in the tAB and femoral shape 7 years post-ACL-reconstruction, but no side-to-side differences in subregional ThC were found between the operated and contra-lateral non-operated knees.

Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system.

OBJECTIVE: Methylation of the promoter region of the estrogen receptor gene alpha (ER alpha) occurs as a function of age in human colon, and results in inactivation of gene transcription. In this study, we sought to determine whether such age-related methylation occurs in the cardiovascular system, and whether it is associated with atherosclerotic disease. METHODS: We used Southern blot analysis to determine the methylation state of the ER alpha gene in human right atrium, aorta, internal mammary artery, saphenous vein, coronary atherectomy samples, as well as cultured aortic endothelial cells and smooth muscle cells. RESULTS: An age related increase in ER alpha gene methylation occurs in the right atrium (range 6 to 19%, R = 0.36, P < 0.05). Significant levels of ER alpha methylation were detected in both veins and arteries. In addition, ER alpha gene methylation appears to be increased in coronary atherosclerotic plaques when compared to normal proximal aorta (10 +/- 2% versus 4 +/- 1%, P < 0.01). In endothelial cells explanted from human aorta and grown in vitro, ER alpha gene methylation remains low. In contrast, cultured aortic smooth muscle cells contain a high level of ER alpha gene methylation (19-99%). CONCLUSIONS: Methylation associated inactivation of the ER alpha gene in vascular tissue may play a role in atherogenesis and aging of the vascular system. This potentially reversible defect may provide a new target for intervention in heart disease.

Neurologic injury in cardiac surgical patients with a history of stroke.

BACKGROUND: Controversy still exists as to whether patients with previous stroke are at increased risk for neurologic complications after heart operations. METHODS: We performed a prospective analysis of 1,000 consecutive patients undergoing cardiac operations requiring cardiopulmonary bypass, without hypothermic circulatory arrest. Of the 1,000 patients, 71 had previously documented stroke (study group); 2 control patients with no history of stroke were selected for each of these patients (control group, n = 142). There were no significant differences between the study and control patients with respect to established risk factors for neurologic complications. RESULTS: Compared with controls, study patients took longer to awaken (12.6 +/- 10.9 versus 3.5 +/- 2.1 hours; p < 0.0001) and longer to extubate (29.5 +/- 29.3 versus 9.1 +/- 5.2 hours; p < 0.001), and had a greater incidence of reintubation (7 of 71, 9.9% versus 2 of 142, 1.4%; p < 0.01) and postoperative confusion (26 of 71, 36.6% versus 7 of 142, 4.9%; p < 0.001). There was a higher incidence of focal neurologic deficit among study patients (31 of 71, 43.7% versus 2 of 142, 1.4%; p < 0.001). These deficits included new stroke (6 of 71, 8.5%) as well as the reappearance of previous deficits (19 of 71, 26.8%) or worsening of previous deficits (6 of 71, 8.5%), without new abnormalities on head computed tomography or magnetic resonance imaging. Study patients with neurologic deficit had longer cardiopulmonary bypass times than did study patients without deficit (146 +/- 48.5 versus 110 +/- 43.3 minutes; p < 0.001). The 30-day mortality rate was greater in study patients than in controls (5 of 71, 7% versus 1 of 142, 0.7%; p < 0.02), with four deaths among the 6 study patients with a new stroke (66.7%). CONCLUSION: This analysis identifies a group of patients at high risk for neurologic sequelae and confirms the vulnerability of the previously injured brain to cardiopulmonary bypass, as evidenced by reappearance or exacerbation of focal deficits in such patients.

North American experience with the Perma-Flow prosthetic coronary graft.

BACKGROUND: The Perma-Flow prosthetic coronary graft is a 5-mm polytetrafluoroethylene tube into which is incorporated a Venturi flow restrictor. An aorto-superior vena caval fistula is created and coronary anastomoses are constructed proximal to the resistor in side-to-side fashion, where arterial pressure is maintained. From November 1992 through December 1995, eight investigational centers in North America have implanted this graft in 40 patients with inadequate autologous alternatives. METHODS: Patients were selected for inclusion in this study if coronary artery bypass grafting was required and adequate autologous conduit to complete revascularization was not available. Operative data were completed by the implantating surgeon and referred to a central center, the Minneapolis Heart Institute, for correlation. Follow-up was conducted by data coordinators at each institution, and follow-up data were obtained directly from these coordinators for inclusion in the study. RESULTS: Patient age ranged from 53 to 82 years, and 15 patients were undergoing reoperations (38%). On each Perma-Flow graft one to four coronary side-to-side anastomoses were constructed. In addition, left internal mammary artery (n = 26), greater saphenous vein (8), right internal mammary artery (4), and gastroepiploic artery (4) were used to complete revascularization. Aortic (2) or mitral valve replacement (1) was also carried out. There were seven operative deaths (18%) and two late deaths (4 and 6 months). After 1 to 37 months (mean, 13 +/- 9 months) of follow-up, 29 of 31 surviving patients are asymptomatic. Echocardiographic heart size has not increased from the postoperative value, indicating limited volume load has not affected heart size. Protocol catheterization (n = 32) in 28 patients 1 week to 1 year postoperatively revealed 7 of 73 studied coronary anastomoses (9.5%) and two distal extensions and resistors were occluded (7%). In 1 patient during sternal debridement at 1 year, no flow was found in the graft. CONCLUSIONS: The Perma-Flow graft is a useful adjunct to complete revascularization in patients with deficient autologous conduit.

Lateral MIDCAB grafting via limited posterior thoracotomy.

OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) is a technique for coronary artery bypass grafting performed under direct vision without sternotomy or cardiopulmonary bypass. The approach has been used principally for primary single vessel grafting of the anterior or inferior coronary circulation. This initial experience presents a new lateral technique for patients with isolated circumflex coronary disease which can be used for both primary and reoperative revascularization with either saphenous vein or a free radial artery conduit. METHODS: Lateral MIDCAB grafting of the circumflex coronary circulation was accomplished over a 33 month period at a single center using saphenous vein or free radial artery as the bypass conduit. Through a limited posterior thoracotomy, the lung is deflated and reflected superiorly. The pericardium is opened below the phrenic nerve to expose an obtuse marginal branch of the circumflex coronary artery. After heparinization, the coronary artery is temporarily occluded proximally and distally with local immobilization and an arteriotomy is performed. The distal anastomosis with running suture is followed by the proximal anastomosis on the descending aorta below the hilum of the lung using a side-biting clamp and radiopaque marker. Intraoperative transit time ultrasound flow measurements confirm adequate graft flow before wound closure. RESULTS: To date, 19 patients have undergone this procedure with a mean follow-up of 12 months. A total of 12 patients received saphenous vein grafts and 7 patients received radial artery grafts. There was one death from arrhythmia on postoperative day 9. There was one elective conversion to conventional sternotomy due to inadequate exposure. Graft flows averaged 33.3 cc/min (range 5-87) and the mean postoperative length of stay was 4.5 days; 4 patients underwent recatheterization; 1 had graft occlusion and 2 received late postoperative catheter-based interventions. All patients are currently free of symptoms. CONCLUSIONS: Lateral MIDCAB grafting provides focused revascularization to the circumflex distribution in both primary and reoperative settings. This approach avoids the hazards of resternotomy, eliminates cardiopulmonary bypass, and hastens postoperative recovery. These early results suggest the technique is effective at relieving symptoms and minimizing perioperative morbidity. Further experience at multiple centers will serve to define the ultimate capabilities of this new approach.

Reoperative MIDCAB grafting: 3-year clinical experience.

OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) is performed under direct vision without sternotomy or cardiopulmonary bypass. The technique is used in reoperative patients through various incisions to revascularize one or two areas of the heart. The internal mammary artery, gastroepiploic artery, radial artery, or saphenous vein are used as graft conduits. METHODS: Anterior coronary targets are grafted with the internal mammary artery via a small anterior thoracotomy. Inferior coronary targets are grafted with the gastroepiploic artery via a small midline epigastric incision. Lateral coronary targets are grafted with radial artery or saphenous vein via a posterior thoracotomy. After partial heparinization, the anastomosis is facilitated by local coronary occlusion and stabilization. Graft follow-up consists of outpatient Doppler examination and selective recatheterization. RESULTS: Between January 1994 and August 1997, 81 patients underwent reoperative MIDCAB grafting. Twenty-one patients (25.9%) had internal mammary grafting, 39 (48.2%) had gastroepiploic grafting, and 21 (25.9%) had lateral grafting with radial artery or saphenous vein. There were nine early deaths (four cardiac, five non-cardiac), five late deaths (three cardiac, two non-cardiac), and nine myocardial infarctions in remaining patients. Sixteen patients underwent recatheterization; there were one graft occlusion, two graft stenoses, and eight anastomotic stenoses. Mean postoperative length of stay was 3.8 days. Ninety percent (55/61) of patients are free of symptoms at a mean follow-up of 7.8 months (range 0-39). CONCLUSIONS: Reoperative MIDCAB grafting avoids the risks of resternotomy, aortic manipulation, and cardiopulmonary bypass. The techniques yield an early patency rate of 94%, which includes eight patients who had postoperative catheter-based interventions. Reoperative MIDCAB grafting had lower rates of supraventricular arrhythmia and transfusion when compared with conventional coronary artery bypass grafting, but did not offer an advantage for mortality, stroke or myocardial infarction. This 3-year experience suggests that while reoperative MIDCAB grafting can effectively revascularize focal areas of the heart, patients should be carefully selected to minimize operative risk.

A new temperature-sensitive contrast mechanism for MRI: Curie temperature transition-based imaging.

A temperature-sensitive MRI contrast mechanism is proposed based on the physical property, the Curie temperature (T(c)), at which a ferromagnetic material transitions to paramagnetic state and vice versa. To evaluate the feasibility of this new contrast mechanism, experiments were performed with solid gadolinium metal, which has a T(c) of 20 degrees C. In phantom and ex vivo experiments, the magnetic susceptibility artifact area decreased with increasing temperature transitioning across T(c) (p < 0.05). Similar results would be expected for a variety of ferromagnetic substances with substance-specific T(c) values. Temperature-sensitive MRI contrast agents harnessing this mechanism may be used to (1) indicate regional attainment of specific temperatures in thermotherapy, (2) render an accumulated contrast agent more or less visible by the external application of appropriate heating or cooling, or (3) quantify tissue temperature based on MR image characteristics and magnetic susceptibility artifact caused by a ferromagnetic-paramagnetic transitioning substance.

Design of practical T2-selective RF excitation (TELEX) pulses.

Traditional T2-based imaging techniques are geared toward imaging long-T2 species. Traditional techniques are, therefore, not optimal in clinical situations where the information of interest lies in the short-T2 species. T2-selective RF excitation (TELEX) is a technique for obtaining a T2-based contrast that highlights short-T2 values while suppressing long-T2 values-opposite to traditional T2 contrast. Previously, TELEX has been demonstrated qualitatively to highlight only very short-T2 values (T2 approximately 0.001 s). When applied to longer T2 values (T2 > or = 0.01 s), TELEX becomes sensitive to deltaB0 non-uniformities. This restricts its application to problems in which the T2 of interest is very short. In this study, TELEX is characterized quantitatively. Furthermore, a bandwidth broadening scheme is developed that reduces the deltaB0 sensitivity of TELEX. This permits the technique to be applied to longer T2 values. The capabilities and limitations of a practical implementation of TELEX are discussed.

Cost analysis of current therapies for limited coronary artery revascularization.

BACKGROUND: Single or double (limited) coronary artery revascularization using percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass (CAB) surgery has recently been enhanced with further innovation in intracoronary stenting and the emergence of minimally invasive direct coronary artery bypass (MIDCAB) grafting. Resource allocation for all modalities is directly dependent on hospitalization costs, length of stay, and clinical results. METHODS AND RESULTS: Four groups of 25 consecutive patients over 9 months at a single center received either PTCA, stenting, MIDCAB, or conventional CAB for single-vessel coronary disease, primarily of the left anterior descending circulation. Day, supply, and procedural charges were evaluated, along with the total hospital charge. Postprocedural length of stay was calculated and compared with a national database. MIDCAB surgery day charges were less than stenting but greater than PTCA, MIDCAB supply charges were the least of all groups, and MIDCAB procedural charges were less than for conventional CAB. Total charges for MIDCAB grafting were less than for stenting but greater than for PTCA. Postprocedural length of stay for MIDCAB patients was equivalent to PTCA patients and significantly less than for stenting or for conventional CAB. CONCLUSIONS: MIDCAB grafting provides a new surgical approach that is comparable in charges to catheter-based interventions. The technique markedly reduces length of stay and perioperative morbidity. The selection of medical or surgical limited coronary revascularization can now be based primarily on clinical outcomes without consideration for associated resource allocation.

Carotid sinus baroreceptor reflex control of respiration.

We have studied the effect of the carotid sinus baroreceptor reflex on respiration in 10 vagotomized, spontaneously breathing, pentobarbital anesthetized dogs. The carotid body chemoreceptor reflex response was eliminated by surgically excluding the carotid bodies from the carotid sinus baroreceptor area. Steady state frequency, tidal volume, and minute ventilation were measured after 25 mm Hg step changes in intrasinus pressure between 50 and 200 mm Hg. Over this range, the step decreases in intrasinus pressure caused concomitant increases in mean arterial pressure from 86 to 182 mm Hg. All of the respiratory response curves were sigmoidal in shape. Decreasing intrasinus pressure from 200 to 50 mm Hg caused respiratory frequency to increase from 4.8 to 9.7/min, and tidal volume to decrease from 704 to 515 ml. The calculated total ventilation, however, increased from 3180 to 4530 ml/min. The time of inspiration decreased from 3.7 to 2.4 seconds, and the time of expiration decreased from 9.8 to 4.1 seconds. These ventilatory responses are shown to be baroreceptor reflex mediated, and not secondary to changes in arterial pressure. These findings indicate that not only does the carotid sinus baroreceptor reflex control arterial pressure, but it also simultaneously influences ventilation, through changes in both respiratory frequency and tidal volume.

Aortic valve replacement in the elderly. Risk factors and long-term results.

OBJECTIVE: The current study was undertaken to determine long-term results of aortic valve replacement (AVR) in the elderly, to ascertain predictors of poor outcome, and to assess quality of life. SUMMARY BACKGROUND DATA: Aortic valve replacement is the procedure of choice for elderly patients with aortic valve disease. The number of patients aged 70 and older requiring AVR continues to increase. However, controversy exists as to whether surgery devoted to this subset reflect a cost-effective approach to attaining a meaningful quality of life. METHODS: This study reviews data on 247 patients aged 70 to 89 years who underwent isolated AVR between 1980 and 1995; there were 126 men (51%) and 121 women (49%). Follow-up was 97% complete (239/247 patients) for a total of 974.9 patient-years. Mean age was 76.2 +/- 4.8 years. Operative mortality and actuarial survival were determined. Patient age, gender, symptoms, associated diseases, prior conditions, New York Health Association class congestive heart failure, native valve disease, prosthetic valve type, preoperative catheterization data, and early postoperative conditions were analyzed as possible predictors of outcome. Functional recovery was evaluated using the SF-36 quality assessment tool. RESULTS: Operative mortality was 6.1% (15/247). Multivariate logistic regression showed that poor left ventricular function and preoperative pacemaker insertion were independent predictors of early mortality. After surgery, infection was predictive of early mortality. Overall actuarial survival at 1, 5, and 10 years was 89.5 +/- 2% (198 patients at risk), 69.3 +/- 3.4% (89 patients at risk), and 41.2 +/- 6% (13 patients at risk), respectively. Cox proportional hazards model showed that chronic obstructive pulmonary disease and urgency of operation were independent predictors of poor long-term survival. Postoperative renal failure also was predictive of poor outcome. Using the SF-36 quality assessment tool, elderly patients who underwent AVR scored comparably to their age-matched population norms in seven of eight dimensions of overall health. The exception is mental health. CONCLUSIONS: Aortic valve replacement in the elderly can be performed with acceptable mortality. Significant preoperative risk factors for early mortality include poor left ventricular function and preoperative pacemaker insertion. Predictors of late mortality include chronic obstructive pulmonary disease and urgency of operation. These results stress the importance of operating on the elderly with aortic valve disease; both long-term survival and functional recovery are excellent.

Bioprosthetic versus mechanical prostheses for aortic valve replacement in the elderly.

BACKGROUND: Many centers advocate bioprosthetic valves in the elderly to avoid anticoagulation, in particular when patient survival is less than the expected valve durability. Because expected survival in the elderly is increasing and age-specific risk of anticoagulation in the elderly is not known, we examined valve- and anticoagulation-related morbidity in elderly patients after aortic valve replacement (AVR) with bioprostheses or mechanical prostheses. METHODS AND RESULTS: Between January 1980 and June 1994, 211 patients age > or = 70 years underwent isolated AVR; there were 109 men (52%) and 102 women (48%). Mean age was 75.9 +/- 4.8 years. Aortic stenosis was present in 194 (92%) patients. Bioprostheses were used in 145 (69%) and mechanical prostheses were used in 66 (31%). Chronic anticoagulation was maintained in all patients with a mechanical valve and in 18 patients (12%) with a bioprosthetic valve. Follow-up data were obtained for 98% (194 of 197) of hospital survivors at a mean follow-up of 3.8 years. Operative mortality was 6.6%; survival at 3 and 5 years was 75.3 +/- 3% and 64.6 +/- 4%, respectively. There was no significant difference in operative or late mortality between patient groups. Rates of freedom from thromboembolic events, endocarditis and anticoagulant-related hemorrhage for bioprosthetic and mechanical valve patients were similar. Prosthetic failure was identified in three bioprosthetic valves (2%); furthermore, the 4 patients in the series who required reoperation had received bioprostheses at the first operation. CONCLUSIONS: In conclusion, (1) elderly patients undergoing isolated AVR can be managed with either mechanical or bioprosthetic valves with similar early and late risk, as long as there are no specific contraindications to anticoagulation; (2) anticoagulation-related risk of hemorrhage is low in this group of elderly patients; and (3) the low but significant risk of reoperation following the use of bioprostheses suggests that mechanical valves may be underused in the elderly.